Ellen Margrethe Hauge

Coupling of Bone Resorption and Formation in Real Time: New Knowledge Gained From Human Haversian BMUs

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • Nicolai Ernlund Lassen, Clinical Cell Biology, Institute of Regional Health Research, University of Southern Denmark, Vejle/Lillebaelt Hospital, Vejle, Denmark.
  • ,
  • Thomas Levin Andersen
  • Gro Grunnet Pløen
  • Kent Søe, Clinical Cell Biology, Institute of Regional Health Research, University of Southern Denmark, Vejle/Lillebaelt Hospital, Vejle, Denmark.
  • ,
  • Ellen Margrethe Hauge
  • Søren Harving, Orthopaedic Surgery Research Unit, Science and Innovation Center, Aalborg University Hospital, Denmark; Department of Clinical Medicine, Aalborg University, Denmark.
  • ,
  • Gete Ester Toft Eschen, g Department of Plastic and Breast Surgery , Aarhus University Hospital , Aarhus , Denmark.
  • ,
  • Jean-Marie Delaisse, Clinical Cell Biology, Institute of Regional Health Research, University of Southern Denmark, Vejle/Lillebaelt Hospital, Vejle, Denmark.

It is well known that bone remodeling starts with a resorption event and ends with bone formation. However, what happens in between and how resorption and formation are coupled remains mostly unknown. Remodeling is achieved by so-called basic multicellular units (BMUs), which are local teams of osteoclasts, osteoblasts, and reversal cells recently proven identical with osteoprogenitors. Their organization within a BMU cannot be appropriately analyzed in common histology. The originality of the present study is to capture the events ranging from initiation of resorption to onset of formation as a functional continuum. It was based on the position of specific cell markers in longitudinal sections of Haversian BMUs generating new canals through human long bones. It showed that initial resorption at the tip of the canal is followed by a period where newly recruited reversal/osteoprogenitor cells and osteoclasts alternate, thus revealing the existence of a mixed "reversal-resorption" phase. Three-dimensional reconstructions obtained from serial sections indicated that initial resorption is mainly involved in elongating the canal and the additional resorption events in widening it. Canal diameter measurements show that the latter contribute the most to overall resorption. Of note, the density of osteoprogenitors continuously grew along the "reversal/resorption" surface, reaching at least 39 cells/mm on initiation of bone formation. This value was independent of the length of the reversal/resorption surface. These observations strongly suggest that bone formation is initiated only above a threshold cell density, that the length of the reversal/resorption period depends on how fast osteoprogenitor recruitment reaches this threshold, and thus that the slower the rate of osteoprogenitor recruitment, the more bone is degraded. They lead to a model where the newly recognized reversal/resorption phase plays a central role in the mechanism linking osteoprogenitor recruitment and the resorption-formation switch. © 2017 American Society for Bone and Mineral Research.

OriginalsprogEngelsk
TidsskriftJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Vol/bind32
Nummer7
Sider (fra-til)1395-1405
Antal sider11
ISSN0884-0431
DOI
StatusUdgivet - jul. 2017

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